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Doctoral Thesis
DOI
10.11606/T.9.2015.tde-26102015-093528
Document
Author
Full name
Janine Baptista Coimbra
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Campa, Ana (President)
Pinto, Frederico Azevedo da Costa
Felicio, Luciano Freitas
Lepique, Ana Paula
Loureiro, Ana Paula de Melo
Title in Portuguese
Ação de metabólitos da via das triptaminas em linhagens de melanomas
Keywords in Portuguese
Melanoma
Metabolismo
Triptofano
Via das triptaminas
Abstract in Portuguese
O triptofano (Trp) é essencial para muitos processos fisiológicos e seu metabolismo apresenta-se alterado em doenças como no câncer. O Trp é degradado por três vias: via das quinureninas; via serotonérgica e via das triptaminas. A primeira está envolvida com a tolerância e o imune escape de células tumorais, já a segunda leva a produção de serotonina e melatonina, com uma diversidade de funções biológicas e que possuem atividades antitumorais reconhecidas. A terceira rota é a menos estudada e a função dos compostos sintetizados ainda é desconhecida. Trabalhos do grupo mostram que a via das triptaminas é ativa em melanomas e que triptamina (TRY) e dimetiltriptamina (DMT), metabólitos produzidos por esta via, também possuem atividade antitumoral. Nosso objetivo é avançar sobre a compreensão de como esta via afeta o metabolismo e crescimento tumoral. Para tanto, estudamos mais detalhadamente a via em linhagens de melanoma. A adição de TRY e DMT nas culturas modificou a produção de compostos das outras rotas de metabolização do Trp. Além disso, TRY e DMT afetaram a invasividade das células tumorais e TRY aumentou a atividade citotóxica de células mononucleares frente a melanomas. Observamos que apesar dos efeitos biológicos da via das quinureninas estar amplamente relacionado a ligação dos metabólitos no receptor de aril hidrocarbonetos, para a via das triptaminas o receptor parece não estar associado com a atividade antitumoral descrita. Nossos resultados apontam para a importância da via das triptaminas na dinâmica tumoral e a necessidade de estudos mais amplos relacionados ao metabolismo do Trp.
Title in English
Action of tryptamines pathway metabolites in melanoma strains.
Keywords in English
Melanoma
Metabolism
Tryptamines pathway
Tryptophan
Abstract in English
Tryptophan (Trp) is essential for many physiological processes and its metabolism is modified in several diseases such as in cancer. TRP is broken down into three pathways: kynurenine path, serotonergic path and tryptamine path. The first is involved in tolerance and immune escape of cancer cells, while the second leads to the production of serotonin and melatonin, which have a variety of biological functions and recognized antitumor activity. The third route is the least studied and the biological function of the synthesized compounds is still unknown. Our group shows that tryptamine path is active in melanomas and tryptamine (TRY) and dimethyltryptamine (DMT), metabolites produced by this route, also have antitumor activity. Our goal is make progress on understanding how tryptamine route affects metabolism and tumor growth. Therefore, we studied in detail this pathway in melanoma cell lines. The addition of TRY and DMT into the cultures leds the production of metabolites of other Trp routes. Moreover, TRY and DMT affect the invasiveness of tumor cells and TRY increased antitumor activity of the immune system against melanomas. We observed that despite biological effects of kynurenine path be largely related to metabolites binding aryl hydrocarbon receptor, for tryptamine pathway the receptor seems not to be associated with the described antitumor activity. Our results point the importance of tryptamine pathway in tumor dynamics and the need for broader studies related to Trp metabolism.
 
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Publishing Date
2015-11-11
 
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